0 42

Cited 0 times in

SPOCK1/SIX1axis promotes breast cancer progression by activating AKT/mTOR signaling

 Ming Xu  ;  Xianglan Zhang  ;  Songnan Zhang  ;  Junjie Piao  ;  Yang Yang  ;  Xinyue Wang  ;  Zhenhua Lin 
 Aging, Vol.13(1) : 1032-1050, 2021-01 
Journal Title
Issue Date
Adenocarcinoma / genetics* ; Adenocarcinoma / metabolism ; Adenocarcinoma / pathology ; Animals ; Breast Neoplasms / genetics* ; Breast Neoplasms / metabolism ; Breast Neoplasms / pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation / genetics* ; Epithelial-Mesenchymal Transition / genetics* ; Female ; Homeodomain Proteins / genetics* ; Homeodomain Proteins / metabolism ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Grading ; Proteoglycans / genetics* ; Proteoglycans / metabolism ; Proto-Oncogene Proteins c-akt / metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases / metabolism ; Tumor Stem Cell Assay
AKT/mTOR signaling pathway ; EMT ; SIX1 ; SPOCK1 ; breast cancer
SPOCK1 is highly expressed in many types of cancer and has been recognized as a promoter of cancer progression. Its regulatory mechanism in breast cancer (BC) remains unclear. This study aimed to explore the precise function of SPOCK1 in BC progression and to identify the mechanism by which SPOCK1 is involved in cell proliferation and epithelial-mesenchymal transition (EMT). Immunohistochemistry (IHC) experiments and database analysis showed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of in vitro and in vivo assays elucidated that altering the SPOCK1 level led to distinct changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 to enhance cell proliferation, cell cycle progression and EMT by activating the AKT/mTOR pathway, whereas inhibition of the AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression. Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, the SPOCK1/SIX1 axis promoted BC progression by activating the AKT/mTOR pathway to accelerate cell proliferation and promote metastasis in BC, so the SPOCK1/SIX1 axis might be a promising clinical therapeutic target for preventing BC progression.
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
Yonsei Authors
Zhang, Xiang Lan(장향란)
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.